The present invention relates to biodegradable organic radical-functionalized polycarbonates for medical applications, and more specifically, to polycarbonates bearing pendant nitroxide radicals for medical applications.
Magnetic resonance imaging (MRI) is a ubiquitous and non-invasive medical imaging technique that is of critical importance to the diagnosis of various human diseases. Today, the most commonly used MRI contrast agents are gadolinium-based complexes containing the highly paramagnetic Gd3+ ion. While these are generally well-tolerated in the majority of patients, there have nevertheless been reports of side effects including a serious condition known as nephrogenic systemic fibrosis. There has thus been significant interest in developing metal-free contrast agents based on paramagnetic organic radicals.
Rajca, et al., “Organic Radical Contrast Agents for Magnetic Resonance Imaging”, J. Am. Chem. Soc (2012), volume 134, pages 15724-15727 disclose a fourth-generation poly(propylenimine) dendrimer peripherally functionalized with hydrophilic poly(ethylene oxide) groups and paramagnetic spirocyclohexyl nitroxide radicals. While this reported ORCA material was found to be an effective contrast agent, its synthesis was multi-step and low yielding. Secondly, the contrast agent is not biodegradable; thus there exists the possibility of accumulation-related toxicity. Finally, the major portion of the contrast agent is composed of poly(propylenimine), which is known to be cytotoxic to human cells.
Therefore, a continuing need exists for biodegradable, non-toxic radical materials for therapeutic and/or diagnostic medical applications.